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«DESPITE the employment of a number of remedies that have been suggeMted for the control and prevention of bleeding in patients with obstructive ...»

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It is true that most investigators obtain a normal bleeding time in the haemorrhagic diathesis of biliary obstruction. The bleeding time in the four patients reported here were consistently normal. In purpura haemorrhagica, when purpura is present, the bleeding time is always prolonged. Is it that the bleeding time as it is ordinarily determined, measures only an inadequate blood platelet formation and that the plunging of a needle to a depth of about 4 mm. into tissue does not test the contractibility of the vessels?

Treatmlenit.-The haemorrhagic dyscrasia of obstructive jaundice is due to liver injury and diminution of liver function. Briefly stated, the treatment most urgently indicated to avoid h3emorrhage lies in the early relief of biliary obstruction.

At the present time, the best index that we have of the tendency of jaundiced patients to bleed is the coagulation time of the blood. The tendency 'to bleed and delay in the extravascular clotting of blood, however, do not always run parallel. That post-operative bleeding may obtain despite reduction of the coagulation time is well known. An unoperated patient referred to in this report died suddenly from extensive haemorrhage into the entire intestinal tract when the clotting time determined on the same day was normal.

llEMORRHAGIC DIATHESIS OF OBSTRUCTIVE JAUNDICE

That the tendency to haemorrhage and dlelay in the clotting of blood in patients with biliary obstruction may remain refractory to all methods of treatment is illustrated in the histories of two of the patients related here.

When both delay in coagulation and the tendency to spontaneous bleeding are present, conservative means of treatment are less effective than when delay in clotting alone is the only stigma of an abnormal haemostasis. Elsewhere,138 the writer has reported the instance of a patient with profound jaundice of three and one-half years' duration, in which no tendency to spontaneous hemorrhage had been manifested. A clotting time of fifty minutes was reduced to an almost normal reading after calcium administration and transfusions. No bile-ducts could be demonstrated at operation and the. patient died five days later. No tendency to bleed was manifested, nlor were any haemorrhages found at the postmortem examination.

At the University Hospital, calcium chloride has been given pre-operatively to all patients with obstructive jaundice as outlined by Walters, for several years. When the clotting of the venous blood of jaundiced patients is delayed, we have found the intravenous injection of calcium chloride to be more effective in the reduction of the delayed coagulation than other remedies.

But when haemorrhages occur post-operatively, we have cause to rely more on the transfusion of unmodified blood by the Kimpton-Brown tube method than on other measures. Anything that improves liver function may have a favorable influence on the tendency to bleed. W. J. Mayo 81 has emphasized the value of the administration of glucose to patients with hepatic insufficiency.

After hepatectomy in dogs, Mann and his associates 80 have been able to prolong the period of survival for several hours following the intravenous injection of glucose. The value of hypertonic solution of glucose as a hemostatic agent has already been referred to.

What is to be done with the patient whose delay in coagulation remains refractory to all the conservative means of treatment? It is stated that to operate in the presence of a persistently delayed coagulation is only to invite disaster.07 ill In haemophilia, patients have a recurring cycle in which the tendency to bleed after trauma is increased. In some phases of the cycle, the coagulation time may be normal, and the patient may manifest little or no tendency to bleed. In obstructive jaundice, in which the factor of biliary obstruction continues to operate, it is not likely in the presence of complete obstruction that the haemorrhagic diathesis may become automatically adjusted, as McVicar and Fitts 76 have suggested. Postponement of the relief of biliary obstruction after transfusion and calcium have failed to bring about a normal blood coagulation, only permits the vicious cycle to become worse. When it can be demonstrated that the obstruction is incomplete, delay may have some virtue. But to continue with conservative measures, when a fair trial has been of no avail in the reduction of delayed clotting, is procrastination that increases the liability to hemorrhage when operation is performed.

Those who withhold from operating on patients with complete biliary obstruction with a persistent delay in the coagulation of the blood point to the

OWEN H. WANGENSTEEN

enormous mortality of operating for the relief of obstructive jaundice due to malignancy. Without operation, however, the outcome is not long delayed and the mortality is always ioo per cent.

In one of the instances reported here operation was withheld because of the ascites, the delayed coagulation of the blood and spontaneous tendency to h2emorrhage. The operative risk in such a patient, of course, would have been great (75 per cent. in the light of compiled statistics 58b) but the postmortem findings certainly indicated that an operative attempt would have been worth while. A small localized carcinoma of the bile-duct was found at the point of union of cystic and hepatic ducts. The ascites was due to biliary obstruction. No metastases were demonstrated.





It is known that a patient may first exhibit the tendency to haemorrhage after the drainage of bile has been established. One such instance is reported here but fortunately the outcome was favorable after repeated transfusions.

Petren 98 reports fatal instances that bled only after drainage had been effected for several days. Such an occurrence suggests that the sudden release of the biliary obstruction may temporarily increase liver damage, diminish liver function, through cedema or other cause, and increase the liability to haemorrhage. The danger of sudden decompression of the distended urinary bladder following chronic retention of urine is, of course, well known. Crile 12 and Reid "'i have already suggested for other reasons gradual decompression of biliary obstruction in chronic icterus. Reid believes that a "serious toxic state" may occasionally occur after the sudden decompression of the common bile-duct of deeply jaundiced patients.

That the important factor in the avoidance of haemorrhage in patients with biliary obstruction lies in the early relief of the obstruction cannot receive too much emphasis. The greater number of patients needing surgery for the relief of obstructive jaundice come to operation when the block in the bile flow has been present for many weeks and even months. Rovsing 104 stated that in unremitting obstructive jaundice of two to three weeks' duration the patient should be submitted to operation at once. Schmieden and Sebening 113 believe that when biliary obstruction has been complete for more than two weeks and delay in coagulation is present that conservative means are of no value in its treatment. Kehr 61 stated that when biliary obstruction has been present for more than five or six weeks, operation, because of the danger of haemorrhage, carries an extremely high and unnecessary risk.

When catarrhal jaundice, which occasionally occurs even at the time of life when operations for the relief of biliary obstruction are common, can be ruled out by a short period of observation. certainly operation should not be deferred, in the presence of increasing jaundice.

In a patient in whom the jaundice is due to cholangitis, a simple decompression operation as advised by Crile 12 would appear to be the operation of choice. When the obstruction is due to a stone in the common bile-duct and can readily be removed, this should be done, but the removal of the gallbladder even though stone-containing or diseased should be deferred to a later date. Unnecessary operating is to be avoided.

H2EMORRHAGIC DIATHESIS OF OBSTRUCTIVE JAUNDICE

In patients in whom a carcinoma of the pancreas is found (or a chronic pancreatitis causing jaundice, a rare occurrence) a cholecysto-duodenostomy is to be performed. When a carcinoma of the bile-ducts is present and excision of the tumor feasible, a hepatico-duodenostomy or an anastomosis employing the gall-bladder should be done. A simple drainage operation (cholecystostomy) in the cases of duct malignancy carries the same mortality as an anastomosis operation, and these patients stand a complete external biliary fistula poorly.

The choice of a suitable anaesthetic agent in the presence of chronic icterus is very important. The avoidance of chloroform needs no emphasis. The occasional occurrence of anuria after operation. on jaundiced patients under ether has prejudiced the writer against its use. It is known, of course, that anuria may obtain in the course of obstructive jaundice, in unoperated patients and it may be that the operation itself is as much responsible for the complication of anuria as is the anaesthesia. But when possible, the operation should be done without ether. The preliminary injection of morphine combined with novocaine anoesthesia of the abdominal wall and the administration of nitrousoxide anesthesia usually gives sufficient relaxation. An adequate incision gives good exposure and expedites the surgical procedure.

SUMMARY AND CONCLUSIONS

The histories of two unoperated patients who died with spontaneous haemorrhages due to biliary obstruction, are reviewed. The instance of another patient is recorded in which fatal bleeding followed the excision of a stricture and reconstruction of the common bile-duct. Another instance is reported in which the patient almost lost his life through the agency of parenchymatous hxemorrhage, when no dyscrasia of coagulation could be demonstrated preoperatively.

It is pointed out that the retention of bile in the organism per se is probably not responsible for the hemorrhage diathesis of obstructive jaundice. The destruction of liver tissue and the diminution of liver function, consequent upon the biliary obstruction, would appear to be the chief etiologic factors.

The tendency to bleed exhibited by patients with obstructive jaundice does not depend on delay in the extravascular clotting of the blood alone.

The blood-vessels as well as the blood itself in this respect are abnormal.

The important principle in the avoidance of haemorrhage lies in the early relief of biliary obstruction. In the reduction of delayed coagulability, the intravenous injection of calcium chloride is the most dependable agent. In the treatment of parenchymatous haemorrhage, after operation, the transfusion of unmodified blood is of most value. In instances of unremitting jaundice in which the delayed clotting remains refractory to all the conservative methods of reduction in the absence of other contraindications, biliary decompression should be done at once.

Haemorrhage following operation for the relief of biliary obstruction is still an important cause of operative mortality.

OWEN H. WANGENSTEEN

REFERENCES

Addis, T.: The Ineffectiveness of Calcium Salts and of Citric Acid as Used to Modify the Coagulation Time of the Blood for Therapeutic Purposes. Brit. Med. Jour., 1909, vol. i, pp. 997-99.

2 Addis, T.: The Coagulation Time of the Blood in Disease. Edinburgh Med. Jour., I9WO, vol. v, pp. 38-53.

3Arnsberger, Ludwig: Die Chirurgische Bedeutung des Icterus zu gleich ein Beitrag zu Pathologie und Chirurgie der tiefen Gallenwege. Von Bruns Beitrage, I906, vol. xlviii, pp. 172-779.

' Boggs, T. R.: UYber Beeinfluszung der Gerinnungszeit des Blutes in lebenden Organismus. D. Arch. f. klin. Med., 1904, vol. lxxix, pp. 539-50.

Bohr, Christian: tCber die Respiration nach Injection von Pepton und Blutgelinfus and uber die Bedeutung einzelner Organe fur die Gerinnbarkeit des Blutes.

Centralbl. f. Physiol., i88o, vol. iii, pp. 251-4.

6 Boitel, W.: Untersuchungen uber die Hemostatische Wirkung der Bluttransfusion.

Arch. f. klin. Chir., I924, vol. cxxxii, pp. 455-63.

Brakefield, J. L., and Schmidt, C. L. A.: Studies on the Synthesis and Elimination of ' Certain Bile Components in Obstructive Jaundice. Jour. Biol. Chem., I926, vol. lxvii, pp. 523-45.

8Buchbinder, W. C., and Kern, R.: Blood Calcium Deficiency in Experimental Obstructive Jaundice. Amer. Jour. of Physiol., 1927, vol. lxxx, pp. 273-77.

9Cantarow, A., Dodek, S. M., and Gordon, B.: Calcium Studies in Jaundice with Special, Reference to the Effect of Parathyroid Extract on the Distribution of Calcium. Arch. Int. Med., 1927, vol. xl, pp. I29-39.

Conradi, I~.: Uber die Beziehung der Autolyse zur Blutgerinnung Beitrage zur Chem. Physiol. und Pathol., i9oi, vol. i, p. I36 (Abstracted in Schmidt's Jahrbuch, 273).

I902, p.

Corin, G., and Ansiaux, G.: Untersuchungen uber Phosphorvergiftung. Viertel Jahrschrift f. Gerichtliche Med., I894, vol. vii, pp. 80-95 and 2I2-225.

2 Crile, G. W.: The Technic of Gall-bladder Surgery in the Presence of Jaundice.

Surg., Gynec. and Obstet., I92I, vol. xxxiii, No. 2, pp. 469-7I.

' Denk, W., and Hellman, I.: Die Verwertung der Koagulationsbestimmung des Blutes in der Chirurgie. Mitteil aus der Grenzgeb d. Med. u. Chir., I909, Vol. xx, 2I8-31.

pp.

4Doyon, M.: Incoagulabilite du Sang provoque par le Chloroforme; R6le du Foie.

Compt. Rendues de la soc. de Biol., 1905, vol. lviii, p. 30.

1idemn.: Contribution a la Etude des Conditions de la Formation de l'Antithrombin~e par le Foie. Ibid., 1910, vol. lxviii, p. 30.

16 Idem.: Secretion par le Foie sous l'Influence du Sang Arteriel normal d'une Substance anticoagulante plus de vingt quatre Heures apres l'Isolement et Lavage du Foie.

Ibid., I9IO, vol. lxix, p. 670.

Idem.: Experiences concernant l'Isolement de la Substance Anticoagulante contenue dans les Organs. Ibid., 19IO, vol. lxix, p. 485.

Idem.: Anthrombine des Organes. Action de la Peptone. Ibid., I919, vol. lxxxii, P. 570.

19 Doyon, M., and Billet, J.: Action elective du Chloroform sur le Foie. Ibid., I905, vol. lviii, p. 853.

2 Doyon, M., and Gautier, C.: Phenomenes tetaniques provoques par l'Anemie arterielle du Foie. Ibid., I90I, vol. lxii, p. 429.

'Idemt.: Exstirpation du Foie et Incoagulabilite du Sang chez la Grenouille. Ibid., I907, lxii, p. 521.



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